Table_2_Host Genetic Determinants of Hepatitis B Virus Infection.doc

Chronic hepatitis B virus (HBV) infection is still a major health problem worldwide. Recently, a great number of genetic studies based on single nucleotide polymorphisms (SNPs) and genome-wide association studies have been performed to search for host determinants of the development of chronic HBV infection, clinical outcomes, therapeutic efficacy, and responses to hepatitis B vaccines, with a focus on human leukocyte antigens (HLA), cytokine genes, and toll-like receptors. In addition to SNPs, gene insertions/deletions and copy number variants are associated with infection. However, conflicting results have been obtained. In the present review, we summarize the current state of research on host genetic factors and chronic HBV infection, its clinical type, therapies, and hepatitis B vaccine responses and classify published results according to their reliability. The potential roles of host genetic determinants of chronic HBV infection identified in these studies and their clinical significance are discussed. In particular, HLAs were relevant for HBV infection and pathogenesis. Finally, we highlight the need for additional studies with large sample sizes, well-matched study designs, appropriate statistical methods, and validation in multiple populations to improve the treatment of HBV infection.

慢性乙型肝炎病毒（hepatitis B virus, HBV）感染仍是全球范围内的重大公共卫生难题。近年来，大量基于单核苷酸多态性（single nucleotide polymorphisms, SNPs）和全基因组关联研究的遗传学研究，旨在探寻慢性HBV感染发生、临床结局、治疗效果以及乙型肝炎疫苗应答的宿主决定因素，研究焦点集中于人类白细胞抗原（human leukocyte antigens, HLA）、细胞因子基因以及Toll样受体。除单核苷酸多态性外，基因插入/缺失与拷贝数变异也与HBV感染相关，但目前已获得的研究结果存在诸多矛盾。在本综述中，我们总结了当前宿主遗传因素与慢性HBV感染、其临床分型、治疗以及乙型肝炎疫苗应答相关的研究现状，并依据结果可靠性对已发表的研究结果进行分类。我们还讨论了上述研究中鉴定出的慢性HBV感染宿主遗传决定因素的潜在作用及其临床意义，其中人类白细胞抗原与HBV感染及发病机制密切相关。最后，我们强调需要开展更多大样本量、研究设计匹配良好、采用合适统计方法且在多人群中进行验证的研究，以优化HBV感染的诊疗策略。